DHFR and non-small cell lung carcinoma: For example, in non-small cell lung cancer, the eccDNA of PLCG2 is upregulated in NSCLC cells, resulting in phosphatidase Cγ2, as a transmembrane signal transduction enzyme, is highly expressed in NSCLC tissues and cells, thereby promoting the progression of NSCLC [17]; the amplification of DHFR gene can also enhance tumor resistance to MTX by increasing the production of DHFR [18].